Neural Mechanisms Connecting Deficient Sleep and Smoking Relapse

Phase 2

Not yet recruiting

Interventions: Behavioral: Experimental health intervention
Drug: Varenicline

Brief Summary: The study aims to investigate whether behavioral interventions promote cessation in adult smokers by ameliorating negative emotions and improving self-control and identify the neural markers of these effects.

Detailed Description: The primary objectives of this study are to compare the effectiveness of two types of behavioral interventions, when combined with varenicline medication, in promoting tobacco cessation among treatment-seeking adults and to elucidate the underlying mechanisms. The secondary objective of this study is to examine sex differences.

Investigators will recruit from two primary sources: 1) community-based recruitment strategies including web and social media ads, lay community members to recruit, and local communication channels; 2) investigators will invite referred patients to the outpatient Tobacco Treatment Service (TTS) at Yale-New Haven Hospital.

All participants will be assigned to one of two behavioral interventions. Both groups will receive treatment with varenicline and attend weekly individual counseling sessions (standard care or cognitive behavioral therapy for insomnia) and wear research-grade sleep actiwatches for passive sleep monitoring.

Participants will have a total of five expected research visits with a scheduled target quit date for Week 4. Participants will undergo MRI at baseline and at Week 4, and attend follow-ups at week 8, 12, and 26.

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

currently enrolled in other treatments
neuropsychiatric exclusions that could interfere with study participation, increase risk of adverse events, and/or induce deficient sleep
medical contraindications for fMRI, varenicline, and/or behavioral treatment
factors that cause deficient sleep and for which behavioral treatment has less benefit
women who are pregnant or nursing

Arm && Interventions

Group	Intervention	Description
Experimental health intervention	Experimental health intervention	Experimental health intervention and varenicline starting 4 weeks before and continuing for 4 weeks after a target quit date for a total of 8 weeks
Experimental health intervention	Varenicline	Experimental health intervention and varenicline starting 4 weeks before and continuing for 4 weeks after a target quit date for a total of 8 weeks
Control health intervention	Varenicline	Control health intervention and varenicline starting 4 weeks before and continuing for 4 weeks after a target quit date for a total of 8 weeks

Primary Outcome Measures

Name	Time	Method
Mean number cigarettes smoked per day	Baseline, week 4, 8, 12, and 26	Mean number cigarettes smoked per day assessed by Time Line Follow Back method
Smoking status	Baseline	Assess expired breath carbon monoxide (CO) at baseline. CO is a standard biomarker of combustible tobacco use, is sensitive to detecting cigarette substitution, and has a typical half-life of 4 hours, and is a standard biomarker for confirming recent smoking abstinence (CO \<5ppm has optimal sensitivity and specificity for biochemically verifying smoking status, including at lower smoking levels).
Quit status	Week 4, 8, 12, and 26	To inquire whether participants have refrained from tobacco use at each visit following their quit date. The quit status will also be verified by assessing expired breath carbon monoxide (CO). CO is a standard biomarker of combustible tobacco use, is sensitive to detecting cigarette substitution, and has a typical half-life of 4 hours, and is a standard biomarker for confirming recent smoking abstinence (CO \<5ppm has optimal sensitivity and specificity for biochemically verifying smoking status, including at lower smoking levels)
Days to smoking relapse	Week 4, 8, 12, and 26	Days of resuming smoking since Week 4 schedule quit date as assessed by the Time Line Follow-back

Secondary Outcome Measures

Name	Time	Method
Change in PROMIS Sleep Disturbance	Baseline, week 4, 8, 12, and 26	The PROMIS Sleep Disturbance is an 8 item self-report of perceptions of sleep quality, sleep depth, and restoration associated with sleep. Each item on the measure is rated on a 5-point scale. PROMIS measures are scored on the T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. High scores mean greater severity of sleep disturbance.
Change in PROMIS Sleep-Related Impairment	Baseline, week 4, 8, 12, and 26	The PROMIS Sleep-Related Impairment is an 8 item self-report of perceptions of alertness, sleepiness, and tiredness during usual waking hours, and the perceived functional impairments during wakefulness. Each item on the measure is rated on a 4-point scale. The score range is 4 to 32. High scores mean greater severity of sleep related impairment.
Change in Insomnia Severity Index	Baseline, week 4, 8, 12, and 26	The Insomnia Severity Index is a 7-item brief screening tool for insomnia. Each item on the measure is rated on a 5-point scale (0-4), with a total score range 0-28. High scores mean greater severity of insomnia.